Azeco Cosmeceuticals

Dosage of finished forms

39. Question: What is the method of Azelaic acid assay in cream as finished product?

Answer: There is no formal standardised method of analysis available for the determination of the assay of Azelaic acid in consumer products. However, to determine the assay of Azelaic acid is common practice for the skilled analytical chemist. The methods described here are not unique but are merely an interpretation of the current standards in analytical chemistry. It is important to distinguish between the vehicles used for Azelaic acid. This may be gels or emulsions (oil-in-water or water-in-oil); usually gels are more easy to analyse than emulsion systems. 1. Gels Gels may contain 1-25% Azelaic acid. The commercially available gels are either configured around acrylic acid- based polymers (carbomers, acrylic acid copolymers), exo-polysaccharides (xanthan gum, sclerotium gum, carrageenans, algins, karaya gum), and/or commercially available cellulose ethers. 1.1. Acrylic acid-based polymers Gels made of cross-linked acrylic acid-based homopolymers are usually identified as carbomers. Direct quantitative determination of Azelaic acid in these gels is not possible; the first step must be to break the gel structure. The matrix has to be opened up and this is best done using a saturated NaCl solution. Carbomers are highly sensitive for electrolytes and the gel particles will “implode”. The viscosity of the original gel is completely eliminated. As it is frequently seen that Azelaic acid is present in those gels as Azelaic acid crystals it is very well possible that the precipitate also will contain Azelaic acid crystals. To avoid that this quantity is not quantitatively determined ethoxydiglycol (Trancutol CG; Gattefossé) is added to the aliquot, double the weight of the sample, to dissolve crystalline Azelaic acid. Subsequently the sample is centrifuged to eliminate the precipitated carbomer, using a standard centrifuge @10,000 rpm during eight minutes. The sample is decanted and the aliquot is than subjected to further analysis. It shall be obvious that the aliquot may also contain other products than Azelaic acid only, and the composition may be rather complex indeed. Quantitative analysis is best done by HPLC, if possible combined with MS (although not strictly necessary). A C18 reversed phase column, 20 cm, is preferred; detection is best done using an UV detector @253,9 nm. To quantitatively determine the assay of Azelaic acid the technique of standard addition is used. For that reason a calibration is made using several, preferably five, concentrations of Azelaic acid dissolved in ethoxy diglycol to determine the response of the detection unit. Subsequently a well-known quantity Azelaic acid is added to the aliquot. Using the calibration curve the quantity Azelaic acid is than easily determined. The methodology is not only valid for carbomers, but is also applicable for all other acrylic & methacrylic acid polymers, usually copolymers with other monomers, provided that the polymers are electrolyte-sensitive. This methodology described for acrylic acid-based polymers is not applicable for exo-polysaccharides and cellulosics as these gels are only limited sensitive for electrolytes. 1.2. Exo-polysaccharides & cellulose ethers The most frequently used exo-polysaccharides (EPS’s) are xanthan gum, carrageenans and alginates. These biopolymers are usually insoluble in lower alcohols such methanol, ethanol, propanol and isopropanol. Gels based on exo-polysaccharides are broken with a lower alcohol of choice; the alcohol shall not be denatured as the denaturant would complicate the product mixture. The amount alco hol needed must be determined on a case-to-case basis. To the mixture of the precipitated EPS an amount ethoxydiglycol double the weight of the sample is added to the aliquot to dissolve crystalline Azelaic acid. From this point onwards the analytical procedure as described in § 1.1 is followed. This methodology is usually also applicable for cellulose ethers: methylcellulose (MC), hydroxyethylcel lulose (HEC), hydroxypropyl methylcellulose (HPMC), but is not applicable for hydroxypropylcellulose (HPC). HPC is a polymer mostly used to gel anhydrous hydrophilic solvents such as ethanol, low molecular weight polyethylene glycols (n=6,8) or diacetin/triacetin.

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